Assessment of Upfront Selection Criteria to Prioritise Patients for Breath-hold Left-sided Breast Radiotherapy.

AIMS: Deep inspiratory breath-hold (DIBH) techniques for left breast and chest wall radiotherapy can reduce cardiac dose. We investigated the use of 'upfront selection' criteria for DIBH based on tumour bed position and whether cardiac shielding was used. MATERIALS AND METHODS: Four methods of selecting patients for DIBH were assessed retrospectively in a cohort of left breast and chest wall treatments. These were: (1) free breathing scan on all patients, selecting DIBH treatment for those with a predicted mean heart dose ≥3 Gy; (2) selective DIBH for those with maximum heart depth (MHD) on free breathing scan ≥1 cm; (3) use of an 'upfront selection process' using tumour bed position as initial selection and measurement of MHD on those not selected upfront; (4) DIBH on all. The methods were assessed on predicted mean heart dose, proportion needing two scans, sensitivity, specificity and the positive and negative predictive values. These were compared with method (1) as the gold standard. RESULTS: In total 134 cases were analysed. The predicted mean heart dose in free breathing was ≥3 Gy in 28 (20.9%). Therefore, applying method (1), 28/134 (20.9%) would be selected for DIBH treatment. Applying method (2), 66/134 (49.2%) would be selected for DIBH treatment, all requiring two scans. Of these, 40/66 (60.6%) would receive < 3 Gy in free breathing so are over-selected; 2/68 (2.9%) would have received >3 Gy in free breathing so failed to be selected. Selection using method (3) was similar to method (2), but only five patients required two planning scans; 61/134 (45.5%) cases would be selected for DIBH upfront and 5/134 (3.7%) after initial free breathing scan; 42/66 (63.6%) of those selected for DIBH treatment would receive <3 Gy in free breathing and 4/68 not selected (6%) would receive >3 Gy in free breathing. For methods (2) and (3) most patients not selected for DIBH would have had a mean heart dose of ≤3 Gy (64/68, 90%). Using method (3), 86% (95% confidence interval 67-96%) of patients with a mean heart dose >3 Gy would be selected for DIBH treatment. The estimated mean and standard error for the area under the receiver operator characteristic curve for MHD as a predictor for mean heart dose was 0.85 (0.03). CONCLUSION: This study supports the use of proposed an 'upfront selection process' as a means of selecting patients for treatment with DIBH and avoiding two radiotherapy planning scans. Calculation of MHD can be used as a surrogate for mean heart dose in the selection of cases for DIBH.

Adequacy of diagnostic tests and surgical management of symptomatic invasive lobular carcinoma of the breast.

INTRODUCTION: Invasive lobular carcinoma (ILC) presents diagnostic and therapeutic challenges as it produces subtle radiological changes. It has been suggested that it is not suitable for breast conserving surgery (BCS). The aim of this study was to ascertain the diagnostic adequacy of modern mammography and ultrasonography in the context of a fast track symptomatic diagnostic clinic in the UK. It also sought to compare the mastectomy, re-excision and BCS rates for ILC with those for invasive ductal carcinoma (IDC). METHODS: A retrospective analysis of prospectively collected data was carried out on all new symptomatic cancers presenting to the one-stop diagnostic clinic of a single breast unit between 1998 and 2007. RESULTS: Compared with IDC, ILC was significantly larger at presentation (46mm vs 25mm), needed re-excision after BCS more often (38.8% vs 22.3%) and required mastectomy more frequently (58.8% vs 40.8%). Although mammography performs poorly in diagnosing ILC compared with IDC, when combined with ultrasonography, sensitivity of the combined imaging was not significantly different between these two histological types. CONCLUSIONS: Provided ultrasonography is performed, standard radiological imaging is adequate for initial diagnosis of symptomatically presenting ILC but some additional preoperative workup should clearly be employed to reduce the higher number of reoperations for this histological type.

Sentinel lymph node biopsy after neo-adjuvant chemotherapy in patients with breast cancer: Are the current false negative rates acceptable?

The advent of sentinel lymph node biopsy has revolutionised surgical management of axillary nodal disease in patients with breast cancer. Patients undergoing neo-adjuvant chemotherapy for large breast primary tumours may experience complete pathological response on a previously positive sentinel node whilst not eliminating the tumour from the other lymph nodes. Results from 2 large prospective cohort studies investigating sentinel lymph node biopsy after neo-adjuvant chemotherapy demonstrate a combined false negative rate of 12.6-14.2% and identification rate of 80-89% with the minimal acceptable false negative rate and identification rate being set at 10% and 90%, respectively. A false negative rate of 14% would have been classified as unacceptable when compared to the figures obtained by the pioneers of sentinel lymph node biopsy which was 5% or less.

Microarray-based comparative genomic hybridisation of breast cancer patients receiving neoadjuvant chemotherapy.

We analysed the molecular genetic profiles of breast cancer samples before and after neoadjuvant chemotherapy with combination doxorubicin and cyclophosphamide (AC). DNA was obtained from microdissected frozen breast core biopsies from 44 patients before chemotherapy. Additional samples were obtained before the second course of chemotherapy (D21) and after the completion of the treatment (surgical specimens) in 17 and 21 patients, respectively. Microarray-based comparative genome hybridisation was performed using a platform containing approximately 5800 bacterial artificial chromosome clones (genome-wide resolution: 0.9 Mb). Analysis of the 44 pretreatment biopsies revealed that losses of 4p, 4q, 5q, 12q13.11-12q13.12, 17p11.2 and 17q11.2; and gains of 1p, 2p, 7q, 9p, 11q, 19p and 19q were significantly associated with oestrogen receptor negativity. 16q21-q22.1 losses were associated with lobular and 8q24 gains with ductal types. Losses of 5q33.3-q4 and 18p11.31 and gains of 6p25.1-p25.2 and Xp11.4 were associated with HER2 amplification. No correlations between DNA copy number changes and clinical response to AC were found. Microarray-based comparative genome hybridisation analysis of matched pretreatment and D21 biopsies failed to identify statistically significant differences, whereas a comparison between matched pretreatment and surgical samples revealed a statistically significant acquired copy number gain on 11p15.2-11p15.5. The modest chemotherapy-driven genomic changes, despite profound loss of cell numbers, suggest that there is little therapeutic selection of resistant non-modal cell lineages.

Good clinical response of breast cancers to neoadjuvant chemoendocrine therapy is associated with improved overall survival.

BACKGROUND: We present extended follow-up from a prospective randomised trial evaluating the role of neoadjuvant chemoendocrine therapy in the treatment of operable breast cancer. PATIENTS AND METHODS: 309 women were randomised to primary surgery followed by eight cycles of adjuvant mitoxantrone, methotrexate with tamoxifen (2MT) or 2MT with mitomycin-C (3MT) versus the same regimen for four cycles before followed by four cycles after surgery. For this analysis the median follow-up of patients was 112 months. RESULTS: After 10 years follow-up there is still no statistically significant difference in disease-free survival (DFS) (71% versus 71%) or overall survival (OS) (63% versus 70%) when comparing adjuvant versus neoadjuvant treatment, respectively. Of 144 evaluable patients in the neoadjuvant arm, 74 achieved a good clinical response and 70 patients achieved a poor clinical response. Good responders had a superior DFS (80% versus 64%, P=0.01) and OS (77% versus 63%, P=0.03) compared to poor responders. CONCLUSIONS: At 10 years, neoadjuvant and adjuvant treatment continue to have equivalent OS and DFS. Good clinical response to neoadjuvant chemotherapy is associated with superior DFS and OS. This supports the use of clinical response of primary breast cancer to neoadjuvant therapy as a surrogate marker of survival benefit.

Pattern of local recurrence after conservative surgery and radiotherapy for soft tissue sarcoma.

PURPOSE: Over the past three decades our centre has adopted a policy of conservative surgery followed by adjuvant radicaldose radiotherapy for medium-and high-grade soft tissue sarcomas. For all cases of local recurrence following this treatment we aimed to define the spatial relationship between sites of recurrence and the positions of the phase 1 and 2 radiotherapy volumes. PATIENTS: We identified 25 cases of local recurrence recorded on our soft tissue sarcoma database between 1986 and 1999 inclusive. We excluded patients with macroscopic residual disease following surgery. Most patients were treated with a phase I volume corresponding to the entire muscle compartment (50 Gy in 25 fractions over 5 weeks) and a phase II volume corresponding to the tumour bed (10 Gy in five fractions). Six of the patients were treated according to a hyperfractionated regimen. METHODS: For each case we reviewed the diagnostic imaging, planning radiographs and prescription sheets. We audited whether treatment had been given according to protocol and defined whether recurrence had arisen in the phase 1 volume, phase 2 volume or 'out of field'. RESULTS: Four (16%) patients recurred within the phase I volume, 17 (68%) recurred within the phase II volume and four (16%) outside the irradiated volume including one marginal recurrence. In six patients there had been deviation from our radiotherapy protocol (usually unavoidable) including all three true out of field recurrences. DISCUSSION: The majority of recurrences occur in the phase 2 volume. Prospective multi-centre data collection and, ideally, a prospective randomised trial are required to formulate an improved treatment policy with respect to radiotherapy margins and dose.

Management problems in oncology.

Man has evolved sophisticated defence mechanisms over millions of years to combat insertion of foreign DNA into his cells. However, gene therapy carries huge potential for the treatment of cancer. The challenge is therefore to translate our scientific knowledge into a clinical reality.

An examination of needlestick injury rates, hepatitis B vaccination uptake and instruction on 'sharps' technique among medical students.

A 12-question survey designed to examine venepuncture techniques and instruction and uptake of hepatitis B vaccination was completed by 172 of the 275 medical students to whom it was distributed (a response rate of 62.5%). Seventy-five injuries were reported, at an average of 0.3 per student per year. Of the respondents, 63% resheathed needles after use, a practice frequently cited as a cause of needlestick injury. However, in this sample resheathing was not significantly associated with a higher or lower injury rate (chi 2 = 2.07, P > 0.1). Of the respondents from the most recent intake, only 20 out of 57 had completed a course of hepatitis B vaccinations prior to the commencement of venepuncture duties. There was almost universal ignorance concerning the correct course of action following 'sharps' injury. Recommendations are made concerning hepatitis B vaccination and teaching strategies for medical students.